Molecular Biology Reports

, Volume 39, Issue 5, pp 6213–6218 | Cite as

Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran

  • Amir Abbas Hamedian
  • Alireza Esteghamati
  • Sina Noshad
  • Mohammad Mozafari
  • Hosein Moin-Tavakkoli
  • Manouchehr Nakhjavani
  • Touraj Mahmoudi
  • Mahfam Nikzamir
  • Reza Safary
  • Abdolrahim Nikzamir


Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction–restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy–Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44–4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200–2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.


Essential hypertension Single nucleotide polymorphism Vascular endothelial growth factor 



We wish to thank all medical and nursing team of Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital for collaboration in this project.

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Coy V (2005) Genetics of essential hypertension. J Am Acad Nurse Pract 17:219–224PubMedCrossRefGoogle Scholar
  2. 2.
    Mein CA, Caulfield MJ, Dobson RJ, Munroe PB (2004) Genetics of essential hypertension. Hum Mol Genet 13 Spec No 1:R169–R175PubMedCrossRefGoogle Scholar
  3. 3.
    Carretero OA, Oparil S (2000) Essential hypertension. Part I: definition and etiology. Circulation 101:329–335PubMedGoogle Scholar
  4. 4.
    Millis RM (2011) Epigenetics and hypertension. Curr Hypertens Rep 13:21–28PubMedCrossRefGoogle Scholar
  5. 5.
    Caulfield M, Munroe P, Pembroke J et al (2003) Genome-wide mapping of human loci for essential hypertension. Lancet 361:2118–2123PubMedCrossRefGoogle Scholar
  6. 6.
    Garcia EA, Newhouse S, Caulfield MJ, Munroe PB (2003) Genes and hypertension. Curr Pharm Des 9:1679–1689PubMedCrossRefGoogle Scholar
  7. 7.
    Samani NJ (2003) Genome scans for hypertension and blood pressure regulation. Am J Hypertens 16:167–171PubMedCrossRefGoogle Scholar
  8. 8.
    Vincenti V, Cassano C, Rocchi M, Persico G (1996) Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation 93:1493–1495PubMedGoogle Scholar
  9. 9.
    Lin TH, Su HM, Wang CL et al (2010) Vascular endothelial growth factor polymorphisms and extent of coronary atherosclerosis in Chinese population with advanced coronary artery disease. Am J Hypertens 23:960–966PubMedCrossRefGoogle Scholar
  10. 10.
    Palmirotta R, Ferroni P, Ludovici G et al (2010) VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension. Clin Biochem 43:1090–1095PubMedCrossRefGoogle Scholar
  11. 11.
    Awata T, Inoue K, Kurihara S et al (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51:1635–1639PubMedCrossRefGoogle Scholar
  12. 12.
    Howell WM, Ali S, Rose-Zerilli MJ, Ye S (2005) VEGF polymorphisms and severity of atherosclerosis. J Med Genet 42:485–490PubMedCrossRefGoogle Scholar
  13. 13.
    Sandrim VC, Palei AC, Cavalli RC et al (2009) Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension. Mol Hum Reprod 15:115–120PubMedCrossRefGoogle Scholar
  14. 14.
    American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28:S37–S42CrossRefGoogle Scholar
  15. 15.
    Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMedGoogle Scholar
  16. 16.
    Esteghamati A, Mansournia N, Nakhjavani M, et al (2011) Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes. Mol Biol Rep 2011 Jul 10. [Epub ahead of print]Google Scholar
  17. 17.
    Plouet J, Schilling J, Gospodarowicz D (1989) Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8:3801–3806PubMedGoogle Scholar
  18. 18.
    Senger DR, Galli SJ, Dvorak AM et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985PubMedCrossRefGoogle Scholar
  19. 19.
    Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611PubMedCrossRefGoogle Scholar
  20. 20.
    Weis SM, Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437:497–504PubMedCrossRefGoogle Scholar
  21. 21.
    Gyurkovics M, Lohinai Z, Gyorfi A et al (2009) Venodilatory effect of vascular endothelial growth factor on rat gingiva. J Periodontol 80:1518–1523PubMedCrossRefGoogle Scholar
  22. 22.
    Wongpiyabovorn J, Hirankarn N, Ruchusatsawat K et al (2011) The association of single nucleotide polymorphism within vascular endothelial growth factor gene with systemic lupus erythematosus and lupus nephritis. Int J Immunogenet 38:63–67PubMedCrossRefGoogle Scholar
  23. 23.
    Lin TH, Wang CL, Su HM et al (2010) Functional vascular endothelial growth factor gene polymorphisms and diabetes: effect on coronary collaterals in patients with significant coronary artery disease. Clin Chim Acta 411:1688–1693PubMedCrossRefGoogle Scholar
  24. 24.
    van der Meer P, De Boer RA, White HL et al (2005) The VEGF +405 CC promoter polymorphism is associated with an impaired prognosis in patients with chronic heart failure: a MERIT-HF substudy. J Card Fail 11:279–284PubMedCrossRefGoogle Scholar
  25. 25.
    Nikzamir A, Esteghamati A, Hammedian AA, Mahmoudi T (2011) The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus. Mol Biol Rep 2011 May 12. [Epub ahead of print]Google Scholar
  26. 26.
    Young HS, Summers AM, Bhushan M et al (2004) Single-nucleotide polymorphisms of vascular endothelial growth factor in psoriasis of early onset. J Invest Dermatol 122:209–215PubMedCrossRefGoogle Scholar
  27. 27.
    Han SW, Kim GW, Seo JS et al (2004) VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology (Oxf) 43:1173–1177CrossRefGoogle Scholar
  28. 28.
    Salvarani C, Boiardi L, Casali B et al (2004) Vascular endothelial growth factor gene polymorphisms in Behçet’s disease. J Rheumatol 31:1785–1789PubMedGoogle Scholar
  29. 29.
    Boiardi L, Casali B, Nicoli D et al (2003) Vascular endothelial growth factor gene polymorphisms in giant cell arteritis. J Rheumatol 30:2160–2164PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Amir Abbas Hamedian
    • 1
  • Alireza Esteghamati
    • 2
  • Sina Noshad
    • 2
  • Mohammad Mozafari
    • 2
  • Hosein Moin-Tavakkoli
    • 2
  • Manouchehr Nakhjavani
    • 2
  • Touraj Mahmoudi
    • 3
  • Mahfam Nikzamir
    • 4
  • Reza Safary
    • 2
  • Abdolrahim Nikzamir
    • 2
    • 5
  1. 1.Health DepartmentSchool of Public Health, Tehran University of Medical SciencesTehranIran
  2. 2.Endocrinology and Metabolism Research Center (EMRC)Vali-Asr Hospital, Tehran University of Medical SciencesTehranIran
  3. 3.Research Center for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
  4. 4.Farzanegan 2 High School, National Organization for Development of Exceptional TalentsTehranIran
  5. 5.Department of Biochemistry, Faculty of MedicineAhvaz Jondi Shapour University of Medical SciencesAhvazIran

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